title: Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia.
abstract: The aim of this study was to identify the clinical parameters of absolutely poor-prognosis patients with chronic critical limb ischemia (AP-CLI). Sixteen no-option CLI patients with arteriosclerosis obliterans: ASO (nine) and non-ASO patients (seven) treated with bone marrow-mononuclear cell implantation (BMI) were analyzed. There were three AP-CLI patients (all ASO). The mRNA expression of several angiogenic factors in the implanted cells was analyzed in comparison with normal donor bone marrow. To observe the response of bone marrow components to hypoxia, normal bone marrow cells were cultured for 24 h in 2.5% O(2), and mRNA expression of angiogenic factors were measured. AP-CLI patients exhibited extraordinary low bone marrow cellularity as well as the percentage of CD34-positive cells. Among angiogenic factors, only VEGF expression was maintained in response to HIF-1, while other factors such as HGF, Ang-1, PLGF, and SDF-1 decreased in the implanted bone marrow cells of the patients with CLI compared to normal bone marrow cells. HIF-1 and all of the five angiogenic factors increased in vitro in response to hypoxia. Thus it is highly likely that angiogenic factors except VEGF do not respond to chronic ischemia in bone marrow in vivo. An organ-protection system against tissue ischemia may be applied for acute hypoxia, but it may be insufficient for chronic ischemia.
authors.affiliation: First Department of Internal Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Oda
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Takuya
authors.initials: T
authors.lastname: Ozawa
authors.forename: Takao
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Noboru
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Tsugumi
authors.initials: T
authors.lastname: Takayama
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Haruo
authors.initials: H
authors.lastname: Hanawa
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Masuko
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002908:Chronic Disease; D016638:Critical Illness; D042783:Endothelial Cells / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D007564:Japan; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000378:metabolism; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D042501:Angiogenic Proteins; D012333:RNA, Messenger